Background: Reproductive risk factors are associated with increased risk of cardiovascular disease (CVD) in women. However, the combined effects of the composite reproductive risk factors on CVD are unknown. This study was performed to construct a reproductive risk score (RRS) to measure reproductive status, examine the association between RRS and CVD, and explore the modification effect of healthy lifestyle on the association in women in the UK Biobank cohort. Methods: The RRS was constructed in 74 141 female participants with data about the items derived for the RRS in the UK Biobank. The RRS was derived from 17 baseline variables, all of which indicated women’s reproductive health status. We defined four categories of RRS status: low-risk group (score 0–1); low-intermediate group (score 2–3); high-intermediate group (score 4–5); and high-risk group (score 6–13). We also constructed a healthy lifestyle score (HLS) with five related factors, and categorized into unhealthy lifestyle group (score: 0–1), intermediate lifestyle group (score: 2–3) and healthy lifestyle group (score: 4–5). Findings: Each point increase in the RRS was associated with a 22% higher risk of CVD (adjusted hazard ratio (aHR): 1.22; 95% confidence interval (CI): 1.16 to 1.28), 23% higher risk of IHD (1.23; 1.17 to 1.31) and 19% higher risk of stroke (1.19; 1.07 to 1.32). The percentage population-attribution risks (PAR%) were 16% (95% CI: 8 to 24) for CVD, 15% (95% CI: 6 to 24) for IHD and 18% (95% CI: 1 to 33) for stroke. A healthy lifestyle significantly attenuated RRS associations with the incidence of CVD and IHD. The attributable proportions due to additive interaction ( P < 0.001) between RRS and HLS were 0.14 (95% CI: 0.07 to 0.22) for CVD and 0.15 (95% CI: 0.09 to 0.23) for IHD, respectively. Interpretation: High RRS was associated with increased risks of CVD, IHD and stroke in female participants in the UK Biobank. The early-stage identification of women with reproductive risk using synthesised indicators and appropriate healthy lifestyle interventions could be useful for the prevention of early CVD and the extension of healthy active life expectancy. Funding: This study was supported by grants from the National Key R&D Program of China (2020YFC2003401) and the High-performance Computing Platform of Peking University. The funders had no role in the study design, data collection, data analysis and interpretation, writing of the report or the decision to submit the article for publication.